Synthesis of Functionalized <i>N</i>-(4-Bromophenyl)furan-2-carboxamides via Suzuki-Miyaura Cross-Coupling: Anti-Bacterial Activities against Clinically Isolated Drug Resistant <i>A. baumannii</i>, <i>K. pneumoniae</i>, <i>E. cloacae</i> and MRSA and Its Validation via a Computational Approach

Abstract

N-(4-bromophenyl)furan-2-carboxamide (3) was synthesized by the reaction furan-2-carbonyl chloride (1) and 4-bromoaniline (2) in the presence of Et3N in excellent yields of 94%. The carboxamide (3) was arylated by employing triphenylphosphine palladium as a catalyst and K3PO4 as a base to afford N-(4-bromophenyl)furan-2-carboxamide analogues (5a-i) in moderate to good yields (43–83%). Furthermore, we investigated the in vitro anti-bacterial activities of the respective compounds against clinically isolated drug-resistant bacteria A. baumannii, K. pneumoniae, E. cloacae and S. aureus. The molecule (3) was found to be the most effective activity against these bacteria, particularly NDM-positive bacteria A. baumannii as compared to various commercially available drugs. Docking studies and MD simulations further validated it, expressing the active site and molecular interaction stability.

Keywords

• amide
• cross-coupling
• anti-bacterial
• resistant
• docking studies
• MD simulations